Bioactive IGF-I Levels in Pediatric Patients Undergoing Growth Hormone Treatment

Overview

This study established pediatric, sex-specific reference ranges for bioactive IGF-I and compared these with total IGF-I and related biomarkers in healthy children and those receiving growth hormone (GH) therapy. Findings indicate that bioactive IGF-I levels generally remain within reference ranges during GH treatment, even when total IGF-I levels are elevated, suggesting bioactive IGF-I may better reflect GH therapy effects.

Background

Growth hormone therapy is used in children with GH deficiency and various non-GHD conditions, with dosing traditionally guided by total IGF-I levels. However, total IGF-I may not reliably indicate treatment efficacy in non-GHD patients and sustained high levels raise safety concerns. IGF-I bioactivity, reflecting receptor activation, may provide a more accurate measure of GH therapy impact. This study aimed to define bioactive IGF-I reference ranges and evaluate its levels in GH-treated pediatric patients.

Data Highlights

Key Findings

• Bioactive IGF-I levels increase with age in healthy children and correlate positively with total IGF-I and IGF-I/IGFBP-3 molar ratio.
• Bioactive IGF-I correlates positively with IGF-I, IGFBP-3, and acid labile subunit measured by LC-MS/MS.
• Bioactive IGF-I and IGF-II levels show a negative correlation.
• Only 13% of GH-treated patients had bioactive IGF-I above +2 standard deviations, compared to 25% for total IGF-I.
• In non-GHD patients, bioactive IGF-I standard deviation scores were significantly lower than total IGF-I scores.
• Monitoring bioactive IGF-I may help optimize GH dosing, particularly in specific patient subgroups.

Clinical Implications

Bioactive IGF-I measurement provides a potentially more accurate assessment of GH therapy effects than total IGF-I, especially in non-GHD pediatric patients. Incorporating bioactive IGF-I monitoring could enhance individualized GH dosing and improve safety by avoiding unnecessary supranormal IGF-I exposure. This approach may refine treatment efficacy evaluation and risk assessment during GH therapy.

Conclusion

Bioactive IGF-I remains within normal ranges in most GH-treated children, even when total IGF-I is elevated, supporting its use as a complementary biomarker to optimize GH therapy. Further research may clarify its role in improving clinical management of pediatric growth disorders.

References

1. Copenhagen Puberty Study III -- Reference Population Data
2. SAGhE Study -- Safety and Appropriateness of Growth Hormone Treatments in Europe
3. Previous Study on Bioactive IGF-I in SGA Children -- 15